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Reactivation of Fetal Hemoglobin for Treating β-Thalassemia and Sickle Cell Disease

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Gene and Cell Therapies for Beta-Globinopathies

Part of the book series: Advances in Experimental Medicine and Biology ((ASGCT,volume 1013))

Abstract

Reactivation of fetal hemoglobin (HbF) in adult hematopoietic cells has the potential for great clinical benefit in patients bearing deleterious mutations in the β-globin gene, such as β-thalassemia and sickle cell disease (SCD), since increasing the production of HbF can compensate for underproduction of β-globin chains (in β-thalassemia) and it can also disrupt sickle hemoglobin polymerization (in SCD). Thus for the past few decades, concerted efforts have been made to identify an effective way to induce the synthesis of HbF in adult erythroid cells for potential therapeutic relief from the effects of these β-globinopathies. Chemical inducers of HbF as well as a number of transcription factors that are able to reactivate HbF synthesis in vitro and in vivo in adult erythroid cells have been identified. However, there has been only limited success in attempts to manipulate either the drugs or regulatory proteins, and in only a fraction of patients, and there is wide variation in individual response to these drugs or transcription factors. These studies highlight the importance for understanding the molecular mechanisms underlying hemoglobin switching so that future studies can be designed to treat these disorders.

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Acknowledgements

We are grateful to our colleagues Andrew D. Campbell and Jordan Shavit (Department of Pediatrics, University of Michigan Medical School) for valuable comments and constructive edits. We also gratefully acknowledge support from NIH grants HL114368 and HL117657 (J.D.E) and the American Heart Association for a Scientist Development Grant (13SDG16950062; S.C.).

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, University of Michigan, 109 Zina Pitcher Place, 3608 BSRB, Ann Arbor, MI, 48109, USA

    Shuaiying Cui

  2. G Carl Huber Professor and Chair Cell and Developmental Biology, University of Michigan, 109 Zina Pitcher Place, 3035 BSRB, Ann Arbor, MI, 48109, USA

    James Douglas Engel

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  1. Shuaiying Cui
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Correspondence to James Douglas Engel .

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Editors and Affiliations

  1. Cincinnati Children’s Hospital, Comprehensive Sickle Cell Program, Cincinnati, Ohio, USA

    Punam Malik

  2. National Institutes of Health and Human Services, Bethesda, Maryland, USA

    John Tisdale

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Cui, S., Engel, J.D. (2017). Reactivation of Fetal Hemoglobin for Treating β-Thalassemia and Sickle Cell Disease. In: Malik, P., Tisdale, J. (eds) Gene and Cell Therapies for Beta-Globinopathies. Advances in Experimental Medicine and Biology(), vol 1013. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7299-9_7

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